Dormant Breast Cancer Micrometastases Reside In Specific Bone Marrow Niches That Regulate Their Transit To and From Bone

Authors: Price et al.

Source: Sci Transl Med, 10.1126/scitranslmed/aad4059.

www.ncbi.nlm.nih.gov/pubmed/27225183

Women with a diagnosis of breast cancer, even if treated with additional medication following surgery, chemotherapy, or radiation, may be at a higher risk for subsequently developing metastatic disease than women without breast cancer. Breast cancer most commonly spreads (metastasizes) to the bone. Up to 30% of breast cancer patients may have clinically silent, tiny bone marrow metastases (micrometastases), meaning that these micrometastases are not functioning to harm the patient. Bone marrow, which is a specific type of tissue that makes blood cells within bones, is a very hospitable location for these micrometastases. However, it is not clear how the breast cancer cells (BCCs) travel between the bone marrow, where they may not be clinically apparent, and the blood, where they may cause symptoms.

Researchers used mouse models to study the relationship between breast cancer micrometastases and specific proteins that act as gatekeepers of the bone marrow. Through various laboratory techniques, scientists discovered that genes of the specific gatekeeper proteins were more prevalent in tumors from women who developed later recurrence of breast disease. Additionally, one specific protein, called E-selectin, was found to help BBCs find their way to bone marrow, much like the way homing pigeons find their destinations.  The BCCs possess structures that bind to E-selectin, which is found within the bone marrow. By blocking the binding of BCC structures to E-selectin, the cells were unable to “home” into the bone marrow.  Furthermore, researchers found that another specific protein helps BCCs “stick” to the bone marrow, while another protein allows the cells to leave the bone marrow.

This study is important because the discoveries may lead to the development of medications that exploit the mechanism of these proteins to force breast cancer cells out of their hiding places in bone marrow, and into the peripheral blood, where they can be targeted by chemotherapy. While barriers still remain in creating such medications, certainly this is a path that will continue to be pursued in the future.